Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.

Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients.

Patient pools and the use of "patient means" are valuable tools in quality control illustrated by a bone-specific alkaline phosphatase assay.

Background: Quality control (QC) is an essential part of clinical biochemistry to ensure that laboratory test results are reliable and correct. Those tests without a defined reference method constitute a special challenge, as is the case with bone-specific alkaline phosphatase (BAP).

Methods And Results: The present study reports an example where a shift in a BAP assay was detected by use of a patient pool and supported by a retrospective calculation of "patient mean", while the external QC and specific assay control material were unaffected by the shift.

Baseline and lifetime alcohol consumption and risk of differentiated thyroid carcinoma in the EPIC study.

Background: Results from several cohort and case-control studies suggest a protective association between current alcohol intake and risk of thyroid carcinoma, but the epidemiological evidence is not completely consistent and several questions remain unanswered.

Methods: The association between alcohol consumption at recruitment and over the lifetime and risk of differentiated thyroid carcinoma was examined in the European Prospective Investigation into Cancer and Nutrition. Among 477 263 eligible participants (70% women), 556 (90% women) were diagnosed with differentiated thyroid carcinoma over a mean follow-up of 11 years.

Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis.

Background: Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs).

Combining plasma measurements and mechanistic modeling to explore the effect of POPs on type 2 diabetes mellitus in Norwegian women.

The number of studies on persistent organic pollutants (POPs) and type 2 diabetes mellitus (T2DM) is growing steadily. Although concentrations of many POPs in humans have decreased substantially, only some studies consider temporal and inter-individual changes in POP concentrations when assessing exposure. Here we combined plasma measurements with mechanistic modeling to generate complementary exposure measures to our single blood draw after disease diagnosis.

Whole-grain products and whole-grain types are associated with lower all-cause and cause-specific mortality in the Scandinavian HELGA cohort.

No study has yet investigated the intake of different types of whole grain (WG) in relation to all-cause and cause-specific mortality in a healthy population. The aim of the present study was to investigate the intake of WG products and WG types in relation to all-cause and cause-specific mortality in a large Scandinavian HELGA cohort that, in 1992-8, included 120 010 cohort members aged 30-64 years from the Norwegian Women and Cancer Study, the Northern Sweden Health and Disease Study, and the Danish Diet Cancer and Health Study. Participants filled in a FFQ from which data on the intake of WG products were extracted.

A processual model for functional analyses of carcinogenesis in the prospective cohort design.

Traditionally, the prospective design has been chosen for risk factor analyses of lifestyle and cancer using mainly estimation by survival analysis methods. With new technologies, epidemiologists can expand their prospective studies to include functional genomics given either as transcriptomics, mRNA and microRNA, or epigenetics in blood or other biological materials. The novel functional analyses should not be assessed using classical survival analyses since the main goal is not risk estimation, but the analysis of functional genomics as part of the dynamic carcinogenic process over time, i.

A statistical framework to model the meeting-in-the-middle principle using metabolomic data: application to hepatocellular carcinoma in the EPIC study.

Metabolomics is a potentially powerful tool for identification of biomarkers associated with lifestyle exposures and risk of various diseases. This is the rationale of the 'meeting-in-the-middle' concept, for which an analytical framework was developed in this study. In a nested case-control study on hepatocellular carcinoma (HCC) within the European Prospective Investigation into Cancer and nutrition (EPIC), serum (1)H nuclear magnetic resonance (NMR) spectra (800 MHz) were acquired for 114 cases and 222 matched controls.

Intake of whole grains and incidence of oesophageal cancer in the HELGA Cohort.

Few prospective studies have investigated the association between whole-grain consumption and incidence of oesophageal cancer. In the Scandinavian countries, consumption of whole grains is high and the incidence of oesophageal cancer comparably low. The aim of this paper was to study the associations between consumption of whole grains, whole-grain products and oesophageal cancer, including its two major histological subtypes.

Subtypes of fruit and vegetables, variety in consumption and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition.

Previously, a lower risk of colorectal cancer was observed with fruit and vegetable consumption in the European Prospective Investigation into Cancer and Nutrition within a follow-up period of 9 years which was not fully supported by a recent meta-analysis. Therefore, we were interested in the relation with extended follow-up, also focusing on single subtypes and a variety of intake of fruit and vegetables. Fruit and vegetable consumption was assessed at baseline.

Glucocorticoid-induced myopathy in the intensive care unit.

Glucocorticoids (GC) are used for intensive care unit (ICU) patients on several indications. We present a patient who was admitted to the ICU due to severe respiratory failure caused by bronchospasm requiring mechanical ventilation and treated with methylprednisolone 240 mg/day in addition to antibiotics and bronchiolytics. When the sedation was lifted on day 10, the patient was awake but quadriplegic.

The Role of Gender in Violence Experienced by Adults With Developmental Disabilities.

Violence against people with developmental disabilities is a highly prevalent yet understudied phenomenon. In particular, there is a paucity of literature surrounding the role of gender and the experiences of men. Using a cross-sectional study design, we surveyed 350 people with diverse developmental disabilities about experiences of abuse, perpetrators of abuse, and their physical and mental health status.

Measurement of absorbed dose to water around an electronic brachytherapy source. Comparison of two dosimetry systems: lithium formate EPR dosimeters and radiochromic EBT2 film.

Interest in high dose rate (HDR) electronic brachytherapy operating at 50 kV is increasing. For quality assurance it is important to identify dosimetry systems that can measure the absorbed doses in absolute terms which is difficult in this energy region. In this work a comparison is made between two dosimetry systems, EPR lithium formate dosimeters and radiochromic EBT2 film.

Transcription outcome of promoters enriched in histone variant H3.3 defined by positioning of H3.3 and local chromatin marks.

Replication-independent histone variant H3.3 is incorporated into distinct genomic regions including promoters. However topology of promoter-associated H3.

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry.

Characterization of Norwegian women eating wholegrain bread.

Objective: To investigate dietary and non-dietary characteristics of wholegrain bread eaters in the Norwegian Women and Cancer study.

Design: Cross-sectional study using an FFQ.

Setting: Women were divided into two groups according to wholegrain bread consumption.

What characterises women who eat potatoes? A cross-sectional study among 74,208 women in the Norwegian Women and Cancer cohort.

Background: Studies of potato consumption have shown that age, region, socioeconomic status, and household structure are important determinants.

Objective: This study aims to map which factors influence potato consumption among women in the Norwegian Women and Cancer (NOWAC) study.

Design: A cross-sectional study using a postal questionnaire among 74,208 NOWAC participants aged 41-70.

Alcohol intake and breast cancer in the European prospective investigation into cancer and nutrition.

Alcohol intake has been associated to breast cancer in pre and postmenopausal women; however results are inconclusive regarding tumor hormonal receptor status, and potential modifying factors like age at start drinking. Therefore, we investigated the relation between alcohol intake and the risk of breast cancer using prospective observational data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Up to 334,850 women, aged 35-70 years at baseline, were recruited in ten European countries and followed up an average of 11 years.

An Exploratory Study of a Computer-Assisted Abuse Awareness and Safety Planning Program for Men With Disabilities: The Men's Safer and Stronger Program.

Interpersonal violence (IPV) is a serious and often unrecognized problem for men with disabilities (MWD). However, abuse awareness programs and outcome measures have not been systematically evaluated in MWD. This article reports findings from an exploratory study (n = 31) of the Safer and Stronger Program for Men with Disabilities (Men's SSP), an audio computer-assisted self-interview (ACASI) abuse awareness program.

Coffee and tea consumption and risk of pre- and postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study.

Introduction: Specific coffee subtypes and tea may impact risk of pre- and post-menopausal breast cancer differently. We investigated the association between coffee (total, caffeinated, decaffeinated) and tea intake and risk of breast cancer.

Methods: A total of 335,060 women participating in the European Prospective Investigation into Nutrition and Cancer (EPIC) Study, completed a dietary questionnaire from 1992 to 2000, and were followed-up until 2010 for incidence of breast cancer.

Distinct features of lamin A-interacting chromatin domains mapped by ChIP-sequencing from sonicated or micrococcal nuclease-digested chromatin.

The nuclear lamina has been shown to interact with the genome through lamina-associated domains (LADs). LADs have been identified by DamID, a proximity labeling assay, and more recently by chromatin immunoprecipitation-sequencing (ChIP-seq) of A- and B-type lamins. LADs form megabase-size domains at the nuclear periphery, they are gene-poor and mostly heterochromatic.

Polyunsaturated fatty acids modify expression of TGF-β in a co-culture model ultilising human colorectal cells and human peripheral blood mononuclear cells exposed to , and .

Commensal bacteria and polyunsaturated fatty acids (PUFAs) have both been shown independently to modulate immune responses. This study tested the hypothesis that the different colonic immunomodulatory responses to commensal () and pathogenic bacteria ( and ) may be modified by PUFAs. Experiments used a Transwell system combining the colorectal cell line HT29, or its mucous secreting sub-clone HT29-MTX, with peripheral blood mononuclear cells to analyse immunomodulatory signalling in response to bacteria, with and without prior treatment with arachidonic acid, eicosapentaenoic acid or docosahexaenoic acid.

Dynamics of smoking-induced genome-wide methylation changes with time since smoking cessation.

Several studies have recently identified strong epigenetic signals related to tobacco smoking. However, an aspect that did not receive much attention is the evolution of epigenetic changes with time since smoking cessation. We conducted a series of epigenome-wide association studies to capture the dynamics of smoking-induced epigenetic changes after smoking cessation, using genome-wide methylation profiles obtained from blood samples in 745 women from 2 European populations.